Interstitial Lung Disease Patterns Research Articles

Pulmonary manifestations of Sjögren's syndrome

Sjögren's syndrome is a chronic inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands. However, extraglandular organ systems may frequently be involved, including the lungs. Although subclinical pulmonary inflammation exists in more than 50% of patients, clinically significant pulmonary involvement affects approximately 10% of patients and may be the first manifestation of the disease. The entire respiratory tract may be involved, with a wide spectrum of manifestations including xerotrachea and bronchial sicca, obstructive small airway disease, various patterns of interstitial lung disease, lymphoinfiltrative or lymphoproliferative lung disease, such as lymphoma (usually of MALT type), pulmonary hypertension, pleural involvement, lung cysts, and pulmonary amyloidosis.

Desquamative Interstitial Pneumonia as the Initial Manifestation of Systemic Sclerosis

Interstitial lung disease (ILD) is a frequent pulmonary complication of systemic sclerosis (SSc), and nonspecific interstitial pneumonia is the most commonly recognized pattern of lung injury in these patients. In this report, we describe a never-smoker female presenting with Raynaud phenomenon and ILD that demonstrated desquamative interstitial pneumonia (DIP) on surgical lung biopsy. After 8 months, she was diagnosed with pulmonary hypertension at which time clinical examinations and serologic findings established the diagnosis of SSc. This case report expands the spectrum of patterns of ILD seen in association with SSc to include DIP.

Comparison of the Incidence and Pattern of Interstitial Lung Disease During Erlotinib and Gefitinib Treatment in Japanese Patients with Non-small Cell Lung Cancer: The Okayama Lung Cancer Study Group Experience

Data comparing the incidence and pattern of interstitial lung disease (ILD) in non-small cell lung cancer patients receiving treatment with gefitinib versus erlotinib, both of which are epidermal growth factor receptor tyrosine kinase inhibitors, are scarce. We investigated the incidence of ILD in Japanese patients treated with gefitinib or erlotinib. We reviewed the clinical records of 209 patients treated with erlotinib in 2008 (cohort A) and 330 treated with gefitinib between 2000 and 2003 (cohort B). Toxicity within the first month of treatment was investigated. The patients in cohort A had fewer known risk factors for ILD (e.g., poor performance status and prior pulmonary fibrosis). ILD was detected in two patients (1.0%) from cohort A and eight patients (2.4%) from cohort B during the first month of treatment. The events were graded as follows: one patient each in grades 1 and 2 (cohort A), and one, one, and six patients in grades 3, 4, and 5, respectively (cohort B). Multivariate analysis revealed that poor performance status and prior pulmonary fibrosis were significantly correlated with the occurrence of ILD, but the type of epidermal growth factor receptor tyrosine kinase inhibitor administered was not. There was a somewhat lower incidence of ILD with erlotinib therapy than with gefitinib therapy, despite no statistically significant difference. Patient selection based on awareness by Japanese physicians of the risk factors for ILD, rather than the type of agent, may explain the difference in ILD incidence between the two treatments.

Interstitielle Lungenerkrankungen

Vasculitis and connective tissue disease are often associated with interstitial lung disease. Involvement of lung parenchyma is found in small vessel vasculitis and mostly in ANCA-associated forms such as Wegener's granulomatosis. In addition to vasculitis and connective tissue disease, rheumatoid arthritis can lead to interstitial lung disease and lung fibrosis. Diagnostic tools include measurement of auto-antibodies, lung function test, chest X-rays and computed tomography of the thorax, as well as bronchoscopy with biopsy and bronchoalveolar lavage. The following article provides an overview of the clinical, histological and radiologic patterns of interstitial lung disease in vasculitis, rheumatoid arthritis and connective tissue disease. Treatment options will also be discussed.

Comparison of incidence and pattern of interstitial lung disease (ILD) during erlotinib and gefitinib treatment in Japanese pts with NSCLC

e19056 Background: Erlotinib was approved in Dec 2007 in Japan, and incidence and pattern of ILD during its therapy for Japanese pts with NSCLC has not still been determined, although we had previously reported the frequency of ILD through the gefitinib treatment [PASCO2004, #7063]. In this study, we intended to elucidate this issue in pts receiving erlotinib therapy. Methods: We reviewed the clinical records of 159 pts who had initiated erlotinib therapy last year (cohort A), and of 330 pts receiving gefitinib between 2000 and 2003 (cohort B) for comparing the incidence and pattern of ILD during the both TKI treatments. Toxicity data during the first months after the initiation of TKIs were obtained. Results: The demographics of 489 pts were as follows; M:63%, Ad:75%, and PS 0–1:69%. None of pts in the cohort B received erlotinib therapy before the gefitinib treatment, whereas 66 of the 159 cohort A pts (42%) were given gefitinib before the erlotinib therapy. In 23% and 28% of the pts in the cohorts A and B, erlotinib and gefitinb treatments were discontinued within 1 month after the initiation of TKI therapy, respectively. Two pts (1.3%) developed ILD in the cohort A during the first month of erlotinib treatment, while 8 ILD-events (2.4%) were observed in the gefitinib therapy (cohort B) during the same treatment period. Both 2 pts who developed ILD during the erlotinib therapy had not had a history of prior gefitinib treatment. The toxicity grades of ILD were as follows: grades 1 and 2 in 1 each (cohort A) and grades 3, 4 and 5 in 1, 1 and 6 pts, respectively (cohort B). Statistically significant factors affecting the occurrence of ILD by multivariate analysis were presence of prior pulmonary fibrosis (OR=37.3, p<0.01) and poor PS (OR=6.4, p=0.02), but type of TKIs was not a significant risk factor for ILD. Conclusions: In this setting, the type of TKIs did not affect the incidence of ILD although its incidence after the initiation of erlotinib was somewhat low as compared with that during gefitinib therapy. In addition, the grade of ILD was less severe in the cohort A. These might be partly due to a patient selection based on the recent awareness of Japanese physicians regarding the risk factors for ILD events who learned it through the gefitinib treatment. No significant financial relationships to disclose.

A Case of a Korean Adult Affected by Type B Niemann-Pick Disease: Secondary Sea-blue Histiocytosis and Molecular Characterization

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.

Subjective Similarity of Patterns of Diffuse Interstitial Lung Disease on Thin-section CT: An Observer Performance Study

The aim of this study was to investigate the subjective similarity for pairs of images with various abnormal patterns of diffuse interstitial lung disease on thin-section computed tomography by experienced radiologists to explore a basis for selecting similar images to assist radiologists' interpretation. Four major patterns (ground-glass opacity, nodular opacity, reticular opacity, and honeycombing) on thin-section computed tomographic images were identified by at least two of three radiologists. One radiologist manually selected 104 image pairs, in which the images in each pair had the same pattern and were similar in appearance. An additional 208 image pairs were randomly selected and evenly divided among the four patterns. These pairs were then rated for subjective similarity (on a continuous scale ranging from 0 = not similar at all to 1.0 = almost identical) by 12 radiologists. For radiologist-selected pairs, the mean similarity rated by the 12 radiologists was 0.72. For randomly selected pairs, the mean similarity was higher for the same pattern (0.47) than for the varying patterns (0.27) (P < .001), and among the same pattern, the mean similarity was 0.63 for ground-glass opacity, 0.58 for honeycombing, 0.45 for nodular opacity, and 0.32 for reticular opacity. The mean standard deviation for similarity ratings on all pairs given by the 12 radiologists was 0.05 (rang, 0.01-0.09). Subjective similarity ratings for pairs of abnormal images can be measured reliably and reproducibly by radiologists and will provide a basis for the selection of similar images to assist radiologists' interpretation.

Feasibility of Automated Quantification of Regional Disease Patterns Depicted on High-Resolution Computed Tomography in Patients with Various Diffuse Lung Diseases

ObjectiveThis study was designed to develop an automated system for quantification of various regional disease patterns of diffuse lung diseases as depicted on high-resolution computed tomography (HRCT) and to compare the performance of the automated system with human readers.Materials and MethodsA total of 600 circular regions-of-interest (ROIs), 10 pixels in diameter, were utilized. The 600 ROIs comprised 100 ROIs that represented six typical regional patterns (normal, ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). The ROIs were used to train the automated classification system based on the use of a Support Vector Machine classifier and 37 features of texture and shape. The performance of the classification system was tested with a 5-fold cross-validation method. An automated quantification system was developed with a moving ROI in the lung area, which helped classify each pixel into six categories. A total of 92 HRCT images obtained from patients with different diseases were used to validate the quantification system. Two radiologists independently classified lung areas of the same CT images into six patterns using the manual drawing function of dedicated software. Agreement between the automated system and the readers and between the two individual readers was assessed.ResultsThe overall accuracy of the system to classify each disease pattern based on the typical ROIs was 89%. When the quantification results were examined, the average agreement between the system and each radiologist was 52% and 49%, respectively. The agreement between the two radiologists was 67%.ConclusionAn automated quantification system for various regional patterns of diffuse interstitial lung diseases can be used for objective and reproducible assessment of disease severity.

Interstitial Lung Diseases in Collagen Vascular Diseases

Different types of interstitial lung diseases (ILDs) develop in collagen vascular diseases (CVDs) such as scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjogren's syndrome, and mixed connective tissue disease. These CVDs represent various histological patterns, including usual interstitial pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis obliterance organizing pneumonia, diffuse alveolar damage, and bronchiolitis. The clinical presentations, prognosis, and response to treatment vary depending on the underlying CVDs, as well as histological patterns of ILDs. In general, the prognosis and survival rate of ILDs in CVDs are better than idiopathic ILDs. Optimal treatment also varies depending on the type of CVDs and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytotoxic drugs are given.

Smoking-related interstitial lung disease

Pulmonary diseases associated with tobacco smoking are a complex group of disorders ranging from chronic obstructive pulmonary disease (COPD) to lung cancer. Interstitial lung diseases (ILDs) have only recently been linked to smoking. The ILDs related to smoking include respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and pulmonary Langerhans cell histiocytosis. The relationship of smoking with each of these entities has been largely established on the weight of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these 3 entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. The importance of making the distinction between them lies in the different clinical management strategies used. Further experimental evidence, including genetic information, may be important in improving our understanding of these diseases.

Usual Interstitial Pneumonia in an Adolescent With ABCA3 Mutations*

Many diverse and frequently idiopathic disorders cause interstitial lung disease (ILD) in children. Although the histologic patterns of ILD in children and adults share similar features, important differences exist in etiology, clinical manifestations, and outcome. Usual interstitial pneumonia (UIP) is the most frequent histologic pattern in adult ILD; however, the characteristic histologic features of UIP have yet to be demonstrated in a child. We report a 15-year-old boy with the UIP pattern of pulmonary fibrosis who had mutations in the adenosine triphosphate-binding-cassette-A3 gene. Discovery of how genetic mutations of proteins involved in surfactant biosynthesis lead to progressive fibrosis will have implications for the understanding of the pathogenesis and clinical manifestations of ILD in both adults and children.

Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue: Imaging Findings in 21 Patients

Few articles have been published on imaging findings of marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue (BALT) of the lung. We present CT scan and 18F-fluorodeoxyglucose (FDG) PET scan findings of the disease. From March 1995 to February 2007, 21 pretreatment patients (male patients, 9; female patients, 12; age range, 35 to 76 years; mean [+/- SD] age, 54 +/- 10.4 years) were seen who had pathologic diagnoses of marginal zone B-cell lymphoma of BALT. After CT scans were reviewed searching for specific patterns and distribution of parenchymal lung lesions, patients were classified as having the following four different patterns: (1) single nodular or consolidative; (2) multiple nodular or areas of consolidation; (3) bronchiectasis and bronchiolitis; and (4) diffuse interstitial lung disease (DILD) patterns. In six patients, in whom PET/CT scanning was performed, the pattern and the extent of maximum standardized uptake values (mSUVs) of FDG uptake were described. A single nodular or consolidative pattern was observed in 7 of 21 (33%) patients, multiple nodular or areas of consolidation were observed in 9 patients (43%), bronchiectasis and bronchiolitis were observed in 3 patients (14%), and DILD was observed in 2 patients (10%). On PET scans (n = 6), lesions showed heterogeneous FDG uptake in five patients and homogeneous uptake in one patient, with mSUVs ranging from 2.2 to 6.3 (mean mSUV, 4.2 +/- 1.48). Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality on CT scans, but single or multiple nodules or areas of consolidation are the main patterns that occur in a majority (76%) of patients. Most lesions show heterogeneous but identifiable FDG uptake on PET scans.

Interstitial Lung Disease in Primary Sjögren Syndrome

Primary Sjögren syndrome (pSS) has been associated with various histologic patterns of interstitial lung disease (ILD). We retrospectively identified 18 patients with pSS and suspected ILD who underwent lung biopsies (14 surgical biopsies and 9 bronchoscopic biopsies) at our institution during a 13-year period from 1992 through 2004. Histopathologic findings were analyzed and correlated with radiologic features and outcome. Median age was 62 years (range, 34 to 78 years), and 15 patients (83%) were women. Most patients presented with dyspnea and cough. Chest radiographs demonstrated bilateral infiltrates, and high-resolution CT revealed abnormalities of various types including ground-glass, consolidation, reticular, and nodular opacities. The major histopathologic patterns included nonspecific interstitial pneumonia (NSIP) [five patients], organizing pneumonia (OP) [four patients], usual interstitial pneumonia (UIP) [three patients], lymphocytic interstitial pneumonia (three patients), primary pulmonary lymphoma (two patients), and diffuse interstitial amyloidosis (one patient). In four patients (three with OP and one with amyloidosis), the diagnosis was established on transbronchial biopsy results. Treatment commonly included prednisone with or without another immunosuppressive agent. During the follow-up period (median, 38 months), most patients improved or remained stable except three patients with UIP, one patient with NSIP, and one patient with amyloidosis. Seven patients (39%) died, including three deaths from acute exacerbation of interstitial pneumonia. A variety of histologic patterns can be seen in patients with pSS-associated ILD. Those with UIP tended to have progression of lung disease. Death from acute exacerbation of interstitial pneumonia may occur in patients with pSS-associated ILD.

Serial chest CT findings in interstitial lung disease associated with polymyositis–dermatomyositis

Objective: A retrospective study was carried out in two institutions to determine serial changes in the pattern, distribution, and extent of interstitial lung disease (ILD) associated with polymyositis (PM)–dermatomyositis (DM) using HRCT. Subjects and methods: Twenty patients with PM–DM and clinical suspicion of ILD who underwent at least two serial HRCT examinations were retrospectively evaluated by two readers. Patients were classified according to the dominant CT pattern which was correlated with clinical evolution and underlying histology when available (n=6). Results: Patients were classified into four groups according to the dominant pattern: ground-glass attenuation and reticulation (group 1, n=9); honeycombing (group 2, n=4); airspace consolidation (group 3, n=4), and normal or almost normal lung (group 4, n=3). Under medical treatment, serial HRCT showed that the extent of areas of ground-glass opacities (group 1) decreased in five patients, stabilized in two, and increased in two. Pathologic findings demonstrated usual interstitial pneumonia (UIP) in two cases and unspecified interstitial pneumonia in one. In group 2, extent of honeycombing increased in three cases and stabilized in one. In group 3, dramatic resolution of airspace consolidation occurred in three cases. Clinical deterioration with extensive consolidation at CT and diffuse alveolar damage (DAD) at histology occurred in one patient of each of the three previous groups. Lesions stayed invisible or progressed slightly in the fourth group. Conclusion: In ILD associated with PM–DM, clinical deterioration and DAD in the follow-up can be observed whatever the HRCT pattern. However, unfavorable evolution is constant when honeycombing is present at the initial CT.

Interstitial Lung disease in Systemic Sclerosis. An HRCT-clinical correlative study

To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Interstitial lung disease in systemic sclerosis.

To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Detection of simulated interstitial lung disease and catheters with selenium, storage phosphor, and film-based radiography.

To evaluate the diagnostic performance of storage phosphor and digital selenium radiography (DSR) with asymmetric and symmetric screen-film systems at different speeds in the detection of simulated interstitial lung disease and catheters. Patterns of simulated interstitial lung disease and catheters were superimposed over an anthropomorphic chest phantom. Hard-copy images were generated at DSR (200-, 400-, and 600-speed), storage phosphor radiography (200- and 400-speed), and asymmetric (400-speed) and symmetric (200- and 400-speed) screen-film imaging. Surface doses were measured, and receiver operating characteristic analyses were performed. No statistically significant differences were found between the detector systems with the same speeds for each interstitial pattern. Significantly poorer results were found at 600-speed DSR than at 200-speed DSR. Detection of catheters and nodules over high-attenuation areas was significantly worse with the symmetric screen-film system than with the other detectors. The surface dose with the DSR system, without a grid, was about 50% less than that of the other detector systems, with grids, at the same speed. No significant difference was found in the diagnostic performance at DSR, storage phosphor radiography, and film-based radiography for simulated interstitial lung disease at corresponding speeds; there was a reduction in the surface dose of about 50% with the 400-speed DSR system.

The value of classifying interstitial pneumonitis in childhood according to defined histological patterns.

Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term 'chronic pneumonitis of infancy' has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile. Twenty-five of 38 open lung biopsies showed an overlapping spectrum of interstitial pneumonitis, including three cases that fulfilled the histological criteria for chronic pneumonitis of infancy. There were 11 cases of reactive pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or follicular bronchiolitis), five of which were associated with abnormalities of the immune system. Four cases were classified as desquamative interstitial pneumonitis and the remaining seven cases were classified as nonspecific interstitial pneumonitis. There were no cases with the histological features of usual interstitial pneumonitis. Most patients responded to steroids but tended to have a residual deficit in lung function. Mortality appeared to be associated with presentation at a young age. Classification of interstitial pneumonitis according to their adult counterparts is appropriate for this younger age group and can provide valuable information for the clinician. The term 'chronic pneumonitis of infancy' refers to a specific histological pattern, but whether it represents a separate disease or a reflection of pulmonary immaturity remains to be proven.

Diffuse Alveolar Damage Associated with Polymyositis

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis (PM-DM), or may occur later in the evolution of disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. We experienced a case of polymyositis associated with diffuse alveolar damage(DAD) that was proven in open lung biopsy. The patient was a 52 year-old woman who was presented with 6 months' duration of generalized ache, edema on ankle and wrist, non-productive cough and mild dyspnea. She had typical symptoms and physical findings of interstitial pneuminitis, and elevated muscle enzyme levels in serum with characteristic histologic findings of myositis on muscle biopsy. She also had typical interstitial lung disease pattern on high resolution CT and restrictive pattern on pulmonary function tests. The findings of open lung biopsy was compatible with diffuse alveolar damage(DAD). She failed to respond to the therapeutic trials with corticosteroid and cyclophosphamide, and finally expired due to acute respiratory distress syndrome.

The Lung in Inflammatory Bowel Disease†

Respiratory involvement in patients with inflammatory bowel disease (IBD) has been reported mainly since 1976. This form of involvement should clearly be separated from interstitial lung disease due to sulfasalazine or mesalamine, although the distinction may be difficult in some cases. We report the data of an ongoing Registry containing 33 cases (23 cases receiving no drug therapy) with ulcerative colitis or, less often, Crohn's disease, who developed varied bronchopulmonary problems. In several cases, the exact diagnosis and the relation of the bronchopulmonary disease to IBD had not been established for many years, thus delaying effective treatment with steroids. In most cases (28/33), respiratory involvement followed the onset of IBD (8 of these 28 cases were postcolectomy), and in the remainder, respiratory manifestations predated the IBD. Patterns of involvement included: 1) Airway inflammation, in the form of subglottic stenosis, chronic bronchitis, severe chronic bronchial suppuration, bronchiectasis, and chronic bronchiolitis. In cases with large airway involvement, endoscopy showed exuberant inflammatory tissue in the airways and narrowing of tracheal and/or bronchial lumen. Histologically, airways were heavily infiltrated by a dense aggregate of inflammatory cells, and there were mucosal ulcerations. 2) Varied patterns of interstitial lung disease, mainly bronchiolitis obliterans with organizing pneumonia, and pulmonary infiltrates and eosinophilia. (3) Miscellaneous other forms of involvement including striking neutrophilic necrotic parenchymal nodules (corresponding histologically to sterile aggregates of neutrophils), and serositis. Steroids were very effective in the majority of cases. Inhaled steroids were of durable benefit in patients with chronic bronchitis, but less often so in those with chronic bronchial suppuration, bronchiectasis, or chronic bronchiolitis. Steroids administered orally led to marked improvement in patients with interstitial lung disease and necrotic nodules, but lacked effectiveness in several patients with severe airway inflammation or chronic bronchiolitis. Intravenous steroids were required in the initial management of life-threatening complications such as asphyxiating subglottic stenosis or extensive interstitial lung disease. Bronchial lavages with methylprednisolone were effective in some patients with severe airway inflammation. Patients with IBD can develop varied inflammatory complications in the lung, and a sizable fraction of these complications is steroid-sensitive.